Impaired post-stroke collateral circulation in sickle cell anemia mice.
Impaired post-stroke collateral circulation in sickle cell anemia mice.
复制标题
DOI：
10.3389/fneur.2023.1215876
复制
发表时间：
2023
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
--
作者：
镰状细胞性贫血（SCA）患者缺血性卒中的发生率很高，但由于担心脑出血，通常被排除在溶栓治疗之外。对脑缺血的适应不良也可能导致SCA的卒中倾向。在这里，我们比较了转基因镰状（SS）小鼠、骨髓移植衍生的SS嵌合体和野生型（AA）对照的中风后皮质侧支循环，因为侧支循环是缺血半暗带内细胞存活的关键因素。此外，已经表明SS小鼠在肢体缺血后发展较差的新侧支灌注。我们在本研究中使用了大脑中动脉（MCA）靶向光血栓形成模型，因为SS小鼠对该模型的耐受性更好，并创建了清晰的梗死核心与梗死周围区域。与AA小鼠相比，SS小鼠在光血栓形成后表现出扩大的梗死和较少的内皮细胞增殖。SS-嵌合体表现出贫血，缺氧诱导的红细胞镰状化，和衰减恢复血流在同侧皮质光血栓形成后。在AA嵌合体中，大脑中动脉与大脑前动脉（ACA）和大脑后动脉（PCA）树之间的边界区域的脑血流量从卒中后对侧水平的44%提高到恢复7 d时的78%。相比之下，SS嵌合体中MCA-ACA和MCA-PCA边缘区域的血流仅在卒中后7天从35%增加到43%。这些发现提示SCA患者存在卒中后侧支循环缺陷。更好地理解这些基础可能为SCA患者提供新的卒中治疗。
Patients with sickle cell anemia (SCA) have a high incidence of ischemic stroke, but are usually excluded from thrombolytic therapy due to concerns for cerebral hemorrhage. Maladaptation to cerebral ischemia may also contribute to the stroke propensity in SCA. Here we compared post-stroke cortical collateral circulation in transgenic sickle (SS) mice, bone marrow grafting-derived SS-chimera, and wildtype (AA) controls, because collateral circulation is a critical factor for cell survival within the ischemic penumbra. Further, it has been shown that SS mice develop poorer neo-collateral perfusion after limb ischemia. We used the middle cerebral artery (MCA)-targeted photothrombosis model in this study, since it is better tolerated by SS mice and creates a clear infarct core versus peri-infarct area. Compared to AA mice, SS mice showed enlarged infarction and lesser endothelial proliferation after photothrombosis. SS-chimera showed anemia, hypoxia-induced erythrocyte sickling, and attenuated recovery of blood flow in the ipsilateral cortex after photothrombosis. In AA chimera, cerebral blood flow in the border area between MCA and the anterior cerebral artery (ACA) and posterior cerebral artery (PCA) trees improved from 44% of contralateral level after stroke to 78% at 7 d recovery. In contrast, blood flow in the MCA-ACA and MCA-PCA border areas only increased from 35 to 43% at 7 d post-stroke in SS chimera. These findings suggest deficits of post-stroke collateral circulation in SCA. Better understanding of the underpinnings may suggest novel stroke therapies for SCA patients.
登录
查看更多内容
影响因子：
29
作者：
Kumar KG;Trevaskis JL;Lam DD;Sutton GM;Koza RA;Chouljenko VN;Kousoulas KG;Rogers PM;Kesterson RA;Thearle M;Ferrante AW Jr;Mynatt RL;Burris TP;Dong JZ;Halem HA;Culler MD;Heisler LK;Stephens JM;Butler AA
通讯作者：
Butler AA
影响因子：
5.6
作者：
Geiseler SJ;Morland C
通讯作者：
Morland C
影响因子：
8.3
作者：
Liebeskind, DS
通讯作者：
Liebeskind, DS
影响因子：
8.3
作者：
Adams, Robert J.
通讯作者：
Adams, Robert J.
影响因子：
8.3
作者：
Lucitti JL;Sealock R;Buckley BK;Zhang H;Xiao L;Dudley AC;Faber JE
通讯作者：
Faber JE